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Bibliography Tag: endocrine disruptors

Kwiatkowski et al., 2016

Kwiatkowski, C. F., Bolden, A. L., Liroff, R. A., Rochester, J. R., & Vandenbergh, J. G.; “Twenty-Five Years of Endocrine Disruption Science: Remembering Theo Colborn;” Environmental Health Perspectives, 2016, 124(9), A151-154; DOI: 10.1289/EHP746


For nearly 30 years, Dr. Theo Colborn (1927–2014) dedicated herself to studying the harmful effects of endocrinedisrupting chemicals on wildlife, humans, and the environment. More recently, she extended this effort to address the health impacts of unconventional oil and gas development. Colborn was a visionary leader who excelled at synthesizing scientific findings across disciplines. Using her unique insights and strong moral convictions, she changed the face of toxicological research, influenced chemical regulatory policy, and educated the public. In 2003, Colborn started a nonprofit organization—The Endocrine Disruption Exchange (TEDX). As we celebrate the 25th anniversary of endocrine disruption science, TEDX continues her legacy of analyzing the extensive body of environmental health research and developing unique educational resources to support public policy and education. Among other tools, TEDX currently uses the systematic review framework developed by the National Toxicology Program at the National Institute of Environmental Health Sciences, to answer research questions of pressing concern. In this article, we pay homage to the tenacious woman and the exemplary contribution she made to the field of environmental health. Recommendations for the future of the field are drawn from her wisdom.  FULL TEXT

de Melo et al., 2019

de Melo, M. S., Nazari, E. M., Joaquim-Justo, C., Muller, Y. M. R., & Gismondi, E.; “Effects of low glyphosate-based herbicide concentrations on endocrine-related gene expression in the decapoda Macrobrachium potiuna;” Environmental Science and Pollution Research International, 2019, 26(21), 21535-21545; DOI: 10.1007/s11356-019-05496-1.


Glyphosate-based herbicides (GBH) are the most used herbicides worldwide and are considered as endocrine-disrupting compounds (EDC) for non-target organisms. However, effects of GBH on their endocrine systems remain poorly understood. Thus, the aim of this study was to assess the effects of low concentrations of Roundup WG(R) on growth and reproduction process molecules in both males and females of the decapod crustacean Macrobrachium potiuna, by the relative transcript expression levels of the ecdysteroid receptor (EcR), the molt-inhibiting hormone (MIH), and the vitellogenin (Vg) genes. Prawns were exposed to three concentrations of GBH (0.0065, 0.065, and 0.28 mg L(-1)) for 7 and 14 days. The results revealed that only in males the three genes transcript levels were influenced by the GBH concentration, time of exposure, and the interaction between the concentrations and time of exposure, suggesting that males were more sensitive to GBH than females. For males, after 7 days of exposure at 0.065 mg L(-1), EcR and MIH were over-expressed, while the Vg expression was only over-expressed after 14 days. The present study highlighted that GBH impacted endocrine systems of M. potiuna. Moreover, EcR and MIH gene expressions could be promising EDC biomarkers of exposure in crustaceans. These results also indicate that GBH concentrations, considered secure by regulatory agencies, should be reviewed to minimize the effects on non-target organisms. FULL TEXT

Stur et al., 2019

Stur, E., Aristizabal-Pachon, A. F., Peronni, K. C., Agostini, L. P., Waigel, S., Chariker, J., Miller, D. M., Thomas, S. D., Rezzoug, F., Detogni, R. S., Reis, R. S. D., Silva Junior, W. A., & Louro, I. D.; “Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines;” Plos One, 2019, 14(7), e0219610; DOI: 10.1371/journal.pone.0219610.


Glyphosate is a broad-spectrum herbicide that is used worldwide. It represents a potential harm to surface water, and when commercially mixed with surfactants, its uptake is greatly magnified. The most well-known glyphosate-based product is Roundup. This herbicide is potentially an endocrine disruptor and many studies have shown the cytotoxicity potential of glyphosate-based herbicides. In breast cancer (BC) cell lines it has been demonstrated that glyphosate can induce cellular proliferation via estrogen receptors. Therefore, we aimed to identify gene expression changes in ER+ and ER- BC cell lines treated with Roundup and AMPA, to address changes in canonical pathways that would be related or not with the ER pathway, which we believe could interfere with cell proliferation. Using the Human Transcriptome Arrays 2.0, we identified gene expression changes in MCF-7 and MDA-MB-468 exposed to low concentrations and short exposure time to Roundup Original and AMPA. The results showed that at low concentration (0.05% Roundup) and short exposure (48h), both cell lines suffered deregulation of 11 canonical pathways, the most important being cell cycle and DNA damage repair pathways. Enrichment analysis showed similar results, except that MDA-MB-468 altered mainly metabolic processes. In contrast, 48h 10mM AMPA showed fewer differentially expressed genes, but also mainly related with metabolic processes. Our findings suggest that Roundup affects survival due to cell cycle deregulation and metabolism changes that may alter mitochondrial oxygen consumption, increase ROS levels, induce hypoxia, damage DNA repair, cause mutation accumulation and ultimately cell death. To our knowledge, this is the first study to analyze the effects of Roundup and AMPA on gene expression in triple negative BC cells. Therefore, we conclude that both compounds can cause cellular damage at low doses in a relatively short period of time in these two models, mainly affecting cell cycle and DNA repair. FULL TEXT

Teleken et al., 2019

Teleken, J. L., Gomes, E. C. Z., Marmentini, C., Moi, M. B., Ribeiro, R. A., Balbo, S. L., Amorim, E. M. P., & Bonfleur, M. L.; “Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring;” Journal of Developmental Origins of Health and Disease, 2019, 1-8; DOI: 10.1017/s2040174419000382.


One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP(R). Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP(R) in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother’s treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP(R) during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus-pituitary-testicular axis regulation in F1 offspring.

Attina et al., 2016

Attina, T. M., Hauser, R., Sathyanarayana, S., Hunt, P. A., Bourguignon, J. P., Myers, J. P., DiGangi, J., Zoeller, R. T., & Trasande, L.; “Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis;” Lancet Diabetes and Endocrinol, 2016, 4(12), 996-1003; DOI: 10.1016/S2213-8587(16)30275-3.


BACKGROUND: Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison.

METHODS: We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (euro1=$1.33).

FINDINGS: The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2.33% of GDP] vs $217 billion [1.28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12.6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion).

INTERPRETATION: EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention.

FUNDING: Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation. FULL TEXT

Perego et al., 2017

Perego, Maria Chiara, Caloni, Francesca, Cortinovis, Cristina, Schutz, Luis F., Albonico, Marco, Tsuzukibashi, Denise, & Spicer, Leon J., “Influence of a Roundup formulation on glyphosate effects on steroidogenesis and proliferation of bovine granulosa cells in vitro,” Chemosphere, 2017, 188, 274-279. DOI: 10.1016/j.chemosphere.2017.09.007.


Glyphosate (N-phosphonomethyl-glycine) is a non-selective systemic herbicide widely used worldwide. The purpose of this study is to determine if glyphosate alone (GLPH) or in formulation with Roundup (G-RU) can affect granulosa cell proliferation and steroid production. Four experiments were conducted. In Exp. 1, 10 and 300 μg/mL of GLPH had no effect (P > 0.05) on cell numbers, estradiol or progesterone production, whereas 10 and 300 μg/mL of G-RU dramatically decreased (P < 0.05) cell numbers and estradiol and progesterone production. In Exp. 2, G-RU at 0.1 μg/mL had no significant effect whereas G-RU at 10 μg/mL decreased (P < 0.05) GC numbers, progesterone and estradiol production. In the absence of IGF1 but presence of FSH, 1 μg/mL of G-RU decreased (P < 0.05) estradiol production, whereas in the presence of IGF1 and FSH, 1 μg/mL of G-RU increased (P < 0.05) cell numbers, progesterone and estradiol production. In Exp. 3, IGF1 significantly increased cell numbers (by 2.8-fold) and estradiol (by 17.8-fold) and progesterone (by 6.1-fold) production. GLPH at 10 μg/mL alone had no significant effect on FSH-induced (i.e., basal) or FSH plus IGF1-induced cell numbers, estradiol or progesterone production. However, G-RU at 10 μg/mL significantly inhibited FSH plus IGF1-induced cell numbers, estradiol and progesterone production by 65%–91%. In Exp. 4, 48 h treatment of G-RU had no significant effect on viability of attached cells. In conclusion, the present studies demonstrate that GLPH and particularly G-RU may have the potential to impair reproductive function in cattle.

Owagboriaye et al., 2019

Owagboriaye, F., Dedeke, G., Ademolu, K., Olujimi, O., Aladesida, A., & Adeleke, M., “Comparative studies on endogenic stress hormones, antioxidant, biochemical and hematological status of metabolic disturbance in albino rat exposed to roundup herbicide and its active ingredient glyphosate,” Environmental Science and Pollution Research International, 2019. DOI: 10.1007/s11356-019-04759-1.


There have been growing concerns and uncertainty about reports attributing the metabolic disturbance induced by a commercial formulation of glyphosate-based herbicide to its active ingredient. We therefore compared the effects of Roundup Original(R) and its active ingredient glyphosate on some hypothalamic-pituitary-adrenal (HPA) hormones and oxidative stress markers, biochemical and hematological profiles in 56 adult male albino rats randomly assigned to seven treatments of eight rats per treatment. The rats were orally exposed to Roundup Original(R) and its active ingredient daily at 3.6 mg/kg body weight (bw), 50.4 and 248.4 mg/kgbw of glyphosate equivalent concentrations for 12 weeks, while control treatment received distilled water. Serum concentrations of corticosterone, adrenocorticotropic hormone, aldosterone and concentration of oxidative stress marker, biochemical and hematological profiles in the blood were determined. Concentrations of corticosterone and aldosterone were significantly higher (p < 0.05) in rats treated with Roundup in a dose-dependent manner. Reduced glutathione concentration, catalase, and butyrylcholinesterase activities reduced significantly in rats treated with Roundup relative to those treated with the active ingredient. Lipid peroxidation was observed in rats treated with Roundup. Biochemical and hematological profiles of rats treated with Roundup were significantly altered (p < 0.05). However, significant changes in only acid phosphatase, lactase dehydrogenase, bilirubin, and white blood cells in rats treated with the active ingredient at 50.4 mg/kg were observed. The severe metabolic disturbance and stress observed in rats treated with the commercial formulation of Roundup herbicide may not be associated with the mild changes induced by the active ingredient.

Chang et al., 2018

Chang, S., Nazem, T. G., Gounko, D., Lee, J., Bar-Chama, N., Shamonki, J. M., Antonelli, C., & Copperman, A. B., “Eleven year longitudinal study of U.S. sperm donors demonstrates declining sperm count and motility,” Fertility and Sterility, 2018, 110(4), e54-e55. DOI: 10.1016/j.fertnstert.2018.07.170.


OBJECTIVE: Physicians and public health experts have been investigating whether there is evidence of deterioration in semen quality.1-3 Investigators who believe in a decline point to the concomitant increase in the incidence of genitourinary abnormalities.3-5 Others have focused on increased exposure to environmental endocrine disruptors and changes in diet and BMI. One obstacle to understanding male fertility is possible geographic variations in semen quality, which may be due to differences in climate, pollution, occupational exposure, lifestyle, and social habits. This study sought to evaluate semen quality in geographically diverse US sperm donors.

DESIGN: Retrospective.

MATERIALS AND METHODS: Semen analyses (SA) from 2007-2017 were examined. The sperm donors (ages 19-38) originated from Los Angeles, Palo Alto, Houston, Boston, Indianapolis and New York City. Total sperm count, average concentration and total motile count were analyzed as a whole and by region. Data was analyzed using a general estimate equation model with an exchangeable working correlation structure.

RESULTS: A total of 124,107 SA specimens were analyzed. Controlling for BMI, there was a decline in total sperm count (b¼-2.9, p<0.01), concentration (b¼-1.76, p<0.01) and total motile sperm count (b¼-2.45, p<0.01) over the 11-year study. There were decreases in SA parameters in all regions except New York City, which showed no change in total sperm count, concentration or total motile sperm count. Boston showed a decline in concentration and total motile sperm count but no difference in total sperm count.

CONCLUSIONS: Changes in our modern environment—chemical exposures or increasingly sedentary lifestyles—may negatively affect spermatogenesis. We demonstrated a time-related decline in semen quality. Given that donors have higher than average sperm counts, these trends would likely be magnified in the general population. If confirmed, these findings would serve as a public health warning, particularly with the simultaneous increase in other male disorders, including testicular cancer.5 The magnitude of semen quality decline varied by region, with only samples from New York City consistent throughout the study. To further investigate geographical differences, future prospective studies should investigate potential causes for this decline. Identifying modifiable risk factors is the first step in determining how to reverse these trend.

Slaby et al., 2019

Slaby, S., Titran, P., Marchand, G., Hanotel, J., Lescuyer, A., Lepretre, A., Bodart, J. F., Marin, M., & Lemiere, S., “Effects of glyphosate and a commercial formulation Roundup(R) exposures on maturation of Xenopus laevis oocytes,” Environmental Science and Pollution Research International, 2019. DOI: 10.1007/s11356-019-04596-2.


Pesticides are often found at high concentrations in small ponds near agricultural field where amphibians are used to live and reproduce. Even if there are many studies on the impacts of phytopharmaceutical active ingredients in amphibian toxicology, only a few are interested in the earlier steps of their life cycle. While their populations are highly threatened with extinction. The aim of this work is to characterize the effects of glyphosate and its commercial formulation Roundup(R) GT Max on the Xenopus laevis oocyte maturation which is an essential preparation for the laying and the fertilization. Glyphosate is an extensively used herbicide, not only known for its effectiveness but also for its indirect impacts on non-target organisms. Our results showed that exposures to both forms of glyphosate delayed this hormone-dependent process and were responsible for spontaneous maturation. Severe and particular morphogenesis abnormalities of the meiotic spindle were also observed. The MAPK pathway and the MPF did not seem to be affected by exposures. The xenopus oocyte is particularly affected by the exposures and appears as a relevant model for assessing the effects of environmental contamination. FULL TEXT

Zhang et al., 2019a

Zhang, Luoping, Rana, Iemaan, Shaffer, Rachel M., Taioli, Emanuela, & Sheppard, Lianne, “Exposure to Glyphosate-Based Herbicides and Risk for Non-Hodgkin Lymphoma: A Meta-Analysis and Supporting Evidence,” Mutation Research/Reviews in Mutation Research, In Press, 2019. DOI: 10.1016/j.mrrev.2019.02.001.


Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that included the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% CI, confidence interval: 1.13–1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we determined a meta-RR for NHL of 1.45 (95% CI: 1.11–1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed available animal and mechanistic studies, which provided supporting evidence for the carcinogenic potential of GBH. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL. Overall, in accordance with evidence from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL. FULL TEXT

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